Is TYR p.Phe207Cys (c.620T>G) pathogenic?

TYR p.Phe207Cys (c.620T>G) is classified Uncertain significance in TYR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: likely pathogenic (0.9868); Absent from gnomAD v4.1.

How common is TYR p.Phe207Cys (c.620T>G) in the general population?

TYR p.Phe207Cys (c.620T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TYR p.Phe207Cys (c.620T>G)?

AlphaMissense predicts likely pathogenic (score 0.9868) — an in-silico prediction, not a clinical call.

TYR p.Phe207Cys

c.620T>G · rs2496530104 · VCV2852097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9868 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9868	likely pathogenic · top 2% in TYR
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -11.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 117 kb · p 0.00089 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TYR
Protein: p.Phe207Cys
Coding: c.620T>G
MANE Select: NM_000372
dbSNP: rs2496530104
Type: single nucleotide variant
Location: chr11:89178573 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB

Full TYR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TYR c.1036+1G>A Pathogenic/Likely pathogenic ★★ same type
TYR c.1036+2T>G Pathogenic ★★ same type
TYR c.1037-1G>A Pathogenic/Likely pathogenic ★★ same type
TYR c.1037-2A>G Pathogenic/Likely pathogenic ★★ same type
TYR c.1037-3C>G Pathogenic/Likely pathogenic ★★ same type
TYR c.1037-7T>A Pathogenic/Likely pathogenic ★★ same type
TYR c.1185-2A>G Pathogenic/Likely pathogenic ★★ same type
TYR c.1366+1G>T Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tyr-p-phe207cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown